Arachidonic acid metabolism and modulation of in vitro anaphylaxis by 5,8,11,14-eicosatetraynoic acid and 9a,12a-octadecadiynoic acid.
1. 5,8,11,14-Eicosatetraynoic acid (ETYA) inhibited the antigen-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. Consistent data were obtained only when the spirals were treated with indomethacin. 2. ETYA did not affect histamine-induced contractions of indomethacin-treated tracheal spirals. 3. 9a, 12a-Octadecadiynoic acid (Ro-3-1314) a potential inhibitor of linoleic acid metabolism, stimulated the antigen-induced contraction of guinea-pig tracheal spirals and the immunological release of slow reacting substances of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments. 4. Both ETYA and Ro-3-1314 inhibited the immunological release of malondialdehyde from guinea-pig lung fragments. 5. The data indicate that the effects of ETYA were due to inhibition of lipoxygenase and the effects of Ro-3-1314 were due to inhibition of cyclo-oxygenase. 6. The results suggest that products of lipoxygenase contribute to the antigen-induced contraction of guinea-pig lung, particularly when cyclo-oxygenase is inhibited. Under these conditions there may be redirection of the metabolism of arachidonic acid to favour production of constrictor products of lipoxygenase such as SRS-A.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D013189:SRS-A; D015117:5,8,11,14-Eicosatetraynoic Acid; C022115:9a-12a-octadecadiynoic acid; D006632:Histamine